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Radiation therapy after conservative breast surgery is an integral part of the treatment of early breast cancer. The aim of radiotherapy is to achieve the best coverage of the Planning Target Volume (PTV), while reducing the dose to the Organs at Risk (OAR). Such goals are not always achievable with the conformal three dimensions plans (3DCRT). Recently, radiation oncologist uses Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) for irradiating the breast. In this study, we compared 3DCRT, IMRT and VMAT for left breast cancer patients in terms of PTV coverage, OAR. We also revised the different dose distribution in 1) different breast volume categories, 2) nodal irradiation versus breast only, and 3) boost versus no boost. Results: The routinely reported dose constrains for the ipsilateral lung and for the heart were not significantly different on comparing the three techniques. While for the contralateral lung, the difference in mean dose was in favor of 3DCRT. In large breast volume, 3DCRT provided a lower Max dose to the contralateral lung and the lowest mean dose to the contralateral breast when compared to IMRT p < 0. 046. In case of no nodal irradiation, the contralateral breast mean dose was lower in 3DCRT in comparison to IMRT and VMAT p < 0.037. When boost dose was given, 3DCRT plans had produced a lower Max dose to the contralateral lung p < 0.017. Conclusion: The three techniques (3DCRT, IMRT, and VMAT) can meet the clinical dosimetry demands of radiotherapy for left breast cancer after conservative surgery, as long as the routinely OARs only (heart and ipsilateral lung) are reported. Our study showed that 3CDRT can provide a lower dose to the contralateral organs (breast and lung), specially, in case of large breast volumes, no nodal irradiation and when a boost is given.

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690,550), a JAK3 inhibitor, ionizing radiation (IR) or in combination. Apoptosis was studied using Annexin V apoptosis detection assay. JAK-STAT phosphorylation patterns post treatment was studied using immunoblotting. Results: Cell viability assays showed that the addition of low dose tofacitinib (200 nM) in both cell lines to low dose (2 Gy) Ionizing Radiation (IR) increased tumor cell death by 2-folds. Combined treatment of IR and tofacitinib increased apoptosis in contrast to treatment with IR or tofacitinib alone. Reduction of downstream JAK-STAT phosphorylation (pSTAT1, pSTAT3, and pSTAT5) was more pronounced in the combined treatment group as compared to IR alone. Conclusion: We were able to demonstrate that abrogation of JAK-STAT pathway through JAK inhibition resulted in improved radiation induced cell death. This was associated with increased apoptosis and down regulation of downstream STATs phosphorylation. A molecularly targeted approach against the JAK-STAT pathway in combination with RT may prove to have clinical utility in future.

Background: Breast cancer is the most common cancer diagnosed worldwide, synchronous bilateral breast cancer accounts for unique entity of the disease, particularly post-operative radiotherapy for Synchronous Bilateral Breast Cancer (SBBC) is challenging with lack of evidence about the best irradiation technique. In this study, we tried to explore the optimum radiotherapy technique regarding the dosimetric parameters. Methods: We recruited 15 SBBC patients in whom post-operative radiotherapy was indicated and we established three plans for each patient using 3DCRT, IMRT and VMAT, and then we compared the three plans as regard target volume coverage parameters and organs at risk (OAR) doses. Results: We found that PTV coverage parameter was superior with IMRT compared with 3DCRT and VMAT in terms of Dmean (p = 0.001), D95% (p = 0.001), D max (p = 0.0001), conformity index (p = 0.0001) and HI (p = 0.0001). Doses to OAR were not significantly different between the three techniques in cardiac dose and LAD maximum dose, but 3DCRT was superior in LAD mean dose (p = 0.03) and lung volume receiving 20 Gy (V20) and 10 Gy (V10) (p = 0.0001), but this difference was non-significant between 3DCRT and IMRT (p = 0.4 and 0.06 respectively), while VMAT led to the highest doses to LAD and lung. Conclusions: IMRT showed the best target coverage parameters in post-operative radiotherapy for SBBC compared with 3DCRT and VMAT. For OAR doses IMRT showed comparable results with 3DCRT, while VMAT delivered a significantly higher dose to OAR.